Identification of allelic variants implicated in neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy and consequential cerebral palsy in individuals of African origin

Abstract

Neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy (NESHIE) is a form of brain injury occurring in neonates due to a shortage of blood flow and consequential oxygen delivery to the brain around the time of birth. Cases of NESHIE often result in severe outcomes including permanent neurological disability or death. NESHIE is a significant health issue in Africa with incidences of up to 35.2 cases per 1000 live births reported. Despite the high incidence of NESHIE in Africa, research on the genetics of NESHIE has primarily focused on individuals of European, Asian and Latin American descent. To date, no African-specific genetic studies on NESHIE have been published.

To lay a foundation for future African-specific genetic case-control studies on NESHIE, this study aimed to determine the allele frequencies and predicted effects of variants within NESHIE genes of interest in the general African population. As a preliminary step, genetic findings on NESHIE from other global populations were catalogued and used to prioritise genes for further study based on their strength of association with NESHIE and involvement in diseases with similar phenotypes. Following the selection of genes of interest, variants within these genes were identified using African-specific sequencing data from the 1000 Genomes Project and the Human Genome Diversity Project. The frequencies and effects of these variants were then analysed to (i) assess the comparability of genetic findings between African populations and European, Asian and Latin American populations, and (ii) identify variants in the genes of interest present in African populations that may warrant further research on their potential involvement in the genetics of NESHIE due to their known or predicted association with disease.

The findings from this study, along with future African-specific research on the genetics of NESHIE, will help determine whether genetic factors contribute to the high incidence of NESHIE in African populations. If such genetic factors are identified, these factors could aid healthcare workers in predicting which neonates are at risk of severe outcomes and facilitate the development of personalised treatment plans.